Over the last decade, The University of Cincinnati College of Medicine has made a major commitment to studies of gene function. Our Transgenic and Knockout Mouse Core Facilities have produced over 600 transgenic mouse strains and over 100 knockout mouse strains. In 1996, a Gene Targeting Core Facility was established which in 1998 alone targeted 27 different genes. In addition, the College of Medicine was at the very forefront in developing Comparative Pathology and Mouse Physiology Core Facilities that have played essential roles in the characterization of dozens of transgenic and knockout strains with phenotypes ranging from preimplantation and congenital defects to cardiovascular disorders to cancer. More recently, an institutional focus on cancer has resulted in the recruitment of numerous clinical and basic science research faculty with outstanding research accomplishments, especially in the area of cancer genetics. With the institutional infrastructure for mouse genetics already in place, participation in the Mouse Models of Human Cancers Consortium will expand considerably our gene discovery and gene function research potential in the area of cancer biology. All of this, coupled with new focus on functional genomics, should give us the ability to make the most of our mouse models of human cancer and to contribute to the future of mouse modeling. We have proposed a focused plan to characterize, manipulate and develop new mouse models of gastrointestinal cancer. Through our participation in the Consortium, we hope to contribute our experience, models and new ideas in order to apply the next generation of functional genomics technologies, advances in drug and therapeutic protein discovery, and pharmacogenomics to the diagnosis and treatment of gastrointestinal cancer.